rs138347314
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001040616.3(LINS1):c.1194A>G(p.Gln398=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,608,822 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0023 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0037 ( 10 hom. )
Consequence
LINS1
NM_001040616.3 synonymous
NM_001040616.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.471
Genes affected
LINS1 (HGNC:30922): (lines homolog 1) The Drosophila segment polarity gene lin encodes a protein, lines, which plays important roles in development of the epidermis and hindgut. This gene encodes a protein containing a lines-like domain. This gene is located on chromosome 15 and clustered with the gene encoding ankyrin repeat and SOCS box-containing protein 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-1.04).
BP6
?
Variant 15-100573679-T-C is Benign according to our data. Variant chr15-100573679-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 211378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.471 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00227 (346/152336) while in subpopulation NFE AF= 0.00395 (269/68032). AF 95% confidence interval is 0.00357. There are 0 homozygotes in gnomad4. There are 155 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LINS1 | NM_001040616.3 | c.1194A>G | p.Gln398= | synonymous_variant | 5/7 | ENST00000314742.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LINS1 | ENST00000314742.13 | c.1194A>G | p.Gln398= | synonymous_variant | 5/7 | 5 | NM_001040616.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00228 AC: 347AN: 152218Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.00211 AC: 522AN: 247486Hom.: 3 AF XY: 0.00228 AC XY: 305AN XY: 133926
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GnomAD4 exome AF: 0.00366 AC: 5331AN: 1456486Hom.: 10 Cov.: 32 AF XY: 0.00363 AC XY: 2627AN XY: 724616
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GnomAD4 genome ? AF: 0.00227 AC: 346AN: 152336Hom.: 0 Cov.: 34 AF XY: 0.00208 AC XY: 155AN XY: 74494
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | LINS1: BP4, BP7, BS2 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 14, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 06, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at